Memorial Sloan Kettering Cancer Center
Our research focuses on understanding how changes in RNA splicing promotes cancer. This is an area of cancer biology in great need of further research and we believe that studying the alterations in RNA splicing in cancer cells will identify many new pathways involved in cancer development.
In addition, one goal of this work is to identify new therapies for cancer by either manipulating RNA processing itself or by targeting one of the abnormal pathways generated by altered splicing in cancer cells.
Omar Abdel-Wahab, MD, is a physician-scientist focused on understanding the genetic causes of hematological malignancies and developing new therapies targeting these genetic alterations. He is a principal investigator of a cancer genetics laboratory in the Human Oncology and Pathogenesis Program and an Attending Physician on the Leukemia Service in the Department of Medicine at Memorial Sloan Kettering Cancer Center. Dr. Abdel-Wahab grew up in North Carolina and completed undergraduate and medical school degrees at Duke University followed by residency in Internal Medicine at Massachusetts General Hospital. He then came to Memorial Sloan Kettering Cancer Center as a post-doctoral research fellow in 2007 and joined the faculty in 2012. He has previously received a Damon Runyon Clinical Scholar Award, a Clinical Scholar Award from the Leukemia & Lymphoma Society, and the Joanne Levy Award for Outstanding Achievement from the American Society of Hematology.
Identification of novel transcripts, pathways, and therapeutic strategies to target spliceosomal-mutant malignancies
Recently, researchers discovered that a significant proportion of patients with a variety of blood cancers spontaneously develop genetic mutations in blood cells affecting a process called RNA splicing. RNA splicing is the process wherein genetic information is read from DNA and then used to make proteins. Mutations affecting RNA splicing are the most common class of mutations in the myelodysplastic syndromes (MDS) and related leukemias developing in patients above age 60. They are also among the most common mutations in chronic lymphocytic leukemia (CLL).
“The Pershing Square Sohn Prize will allow me to explore how the RNA splicing machinery is altered in cancer and how we can utilize this information for new forms of cancer therapy. This funding will allow me to investigate areas of cancer biology which simply have not been explored before.”
Although the discovery of these mutations was a breakthrough, we do not yet fully understand why abnormal RNA splicing results in these cancers. Moreover, we do not yet have therapies that specifically target cancer cells bearing this common class of mutations nor do we have curative therapies for the majority of patients affected by these cancers. Thus, the goals of this proposal are two-fold: (1) to determine how spliceosomal gene mutations result in development of cancer in more detail and (2) to develop new therapies specifically aimed at eradicating cancer cells carrying spliceosomal gene mutations. We hypothesize that spliceosomal mutations cause cancer by affecting the splicing of a relatively small number of very important genes and that we may be able to therapeutically target the specific mis-spliced genes and/or the general alterations in splicing created by these mutations.
“In my perspective, innovation is the exploration of new concepts or development of new techniques to explore problems which have not previously been solved. Given how desperately we need new therapies for cancer, research funding which allows us to take risks to develop new approaches to studying and treating cancer are critically important.”